(Radiographics. 2002;22:601-619.)
© RSNA, 2002
Unusual Primary Lung Tumors: A Radiologic-Pathologic Overview1
Ana Giménez, MD,
Tomás Franquet, MD,
Rosa Prats, MD,
Pilar Estrada, MD,
Jordi Villalba, MD and
Silvia Bagué, MD
1 From the Departments of Radiology (A.G., T.F., R.P., P.E., J.V.) and Pathology (S.B.), Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Sant Antoni M. Claret 167, 08025 Barcelona, Spain. Presented as an education exhibit at the 2000 RSNA scientific assembly. Received September 24, 2001; revision requested October 23 and received December 26; accepted January 9, 2002. Address correspondence to A.G. (e-mail: agimenez@hsp.santpau.es).
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Abstract
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Although the great majority of lung carcinomas are histologically characterized as adenocarcinoma, squamous cell carcinoma, large cell undifferentiated carcinoma, or small cell carcinoma, a variety of rare benign and malignant lung tumors may sporadically affect the lung. Several nonneoplastic tumorlike lesions are seen infrequently but are also part of the differential diagnosis for lung masses. Conventional radiographic findings, although of limited value in the diagnosis of these entities, should be examined carefully when lung tumors are suspected. Computed tomography (CT) is well suited for making a definitive diagnosis of some disease processes. CT helps determine the location and features of the lesions and depicts associated findings to help document the extent of disease. The differential diagnosis can be narrowed when there are typical CT features (eg, the presence of fat in lipoid pneumonia). Although unusual primary lung tumors are difficult to diagnose on the basis of imaging findings alone because such findings are nonspecific in the majority of cases, cross-sectional imaging can play an important role in the diagnostic work-up of these unusual tumors by delineating their extent and directing the radiologist or bronchoscopist to the appropriate biopsy site.
© RSNA, 2002
Index Terms: Amyloidosis, 60.68 • Granuloma, plasma cell, 60.3183 • Lung, nodule • Lung, radiography, 60.11 • Lung neoplasms, 60.319, 60.321, 60.33, 60.34, 60.371 • Lung neoplasms, CT, 60.1211 • Lung neoplasms, diagnosis, 60.1211, 60.1214 • Lung neoplasms, MR, 60.1214 • Lymphomatoid granulomatosis, 60.34 • Pneumonia, lipoid, 60.253
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:
- Describe the radiographic and CT features of a variety of unusual primary lung tumors and pseudotumors.
- Describe the characteristic pathologic features of these lesions.
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Introduction
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A lung tumor may manifest as a solitary nodule or mass or as an endobronchial obstructing lesion. Primary bronchogenic carcinoma from cigarette smoking is by far the most common malignant tumor of the lung and represents a major worldwide health problem. At histologic analysis, almost all primary lung malignancies are adenocarcinoma, squamous cell carcinoma, large cell undifferentiated carcinoma, or small cell carcinoma. However, a variety of uncommon primary tumors and pseudotumors may sporadically affect the lung, although they represent less than 1% of all lung neoplasms (1–3). These rare pulmonary tumors can be either benign or malignant and have a broad spectrum of mesenchymal, epithelial, lymphoreticular, and vascular causes. Several nonneoplastic tumor-like lesions, including exogenous lipoid pneumonia and nodular amyloidosis, are seen infrequently but are also part of the differential diagnosis for lung masses.
Computed tomography (CT) is well suited for making a definitive diagnosis of exogenous lipoid pneumonia when negative attenuation values are demonstrated within the mass. CT also helps determine the precise anatomic location of the mass, the relationship of the lesion to the vascular hilar or mediastinal structures, and the extent of disease.
In this article, we discuss and illustrate the CT features of uncommon benign and malignant lung neoplasms, focusing on the role of CT in the evaluation of these entities. Although there is frequent overlap in the CT appearance of many of these lesions, some have characteristic imaging features that can suggest a specific diagnosis. We also highlight some of the correlative pathologic features with gross or histologic specimens.
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Mesenchymal Tumors
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Primary Liposarcoma
Primary sarcomas of the lung constitute only 3% of lung tumors, and liposarcomas are one of the rarest varieties, with only 11 cases reported in the radiology literature (4,5). Although most primary thoracic liposarcomas occur in the mediastinum, sporadic cases involving the lung, pleura, and chest wall have also been described. Possible pathogenetic factors for the development of primary liposarcoma include malignant degeneration of a pulmonary lipoma and pleuropulmonary asbestosis (5). Primary liposarcoma of the lung has no significant sex predilection, with a reported patient age range of 9–59 years (6,7).
Pathologic Features.—
At gross examination, primary pulmonary liposarcoma appears as a solid nodule or mass with a yellowish cut surface (Fig 1d). At histologic analysis, primary pulmonary liposarcomas are indistinguishable from liposarcomas in other areas of the body. Several distinct histologic types of liposarcomas have been described, including myxomatous, polymorphic, and lipoblastic liposarcomas. Most thoracic liposarcomas exhibit proliferating lipoblasts, with considerable nuclear pleomorphism and a stroma containing a rich capillary network (Fig 1e) (7).
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Figure 1a. Primary lung lipoblastic liposarcoma in a 42-year-old man who presented with mild dyspnea that had been worsening over the past 2 months. (a, b) Posteroanterior (a) and left lateral (b) chest radiographs show a mass in the right lower lobe. (c) Contrast material-enhanced CT scan shows a heterogeneous right lower lobe mass with areas of low attenuation. (d) Photograph of the gross specimen demonstrates a yellowish cut surface related to the presence of fat. Scale is in centimeters. (e) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows proliferation of lipoblasts with vacuolation and nuclear pleomorphism.
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Figure 1b. Primary lung lipoblastic liposarcoma in a 42-year-old man who presented with mild dyspnea that had been worsening over the past 2 months. (a, b) Posteroanterior (a) and left lateral (b) chest radiographs show a mass in the right lower lobe. (c) Contrast material-enhanced CT scan shows a heterogeneous right lower lobe mass with areas of low attenuation. (d) Photograph of the gross specimen demonstrates a yellowish cut surface related to the presence of fat. Scale is in centimeters. (e) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows proliferation of lipoblasts with vacuolation and nuclear pleomorphism.
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Figure 1c. Primary lung lipoblastic liposarcoma in a 42-year-old man who presented with mild dyspnea that had been worsening over the past 2 months. (a, b) Posteroanterior (a) and left lateral (b) chest radiographs show a mass in the right lower lobe. (c) Contrast material-enhanced CT scan shows a heterogeneous right lower lobe mass with areas of low attenuation. (d) Photograph of the gross specimen demonstrates a yellowish cut surface related to the presence of fat. Scale is in centimeters. (e) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows proliferation of lipoblasts with vacuolation and nuclear pleomorphism.
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Figure 1d. Primary lung lipoblastic liposarcoma in a 42-year-old man who presented with mild dyspnea that had been worsening over the past 2 months. (a, b) Posteroanterior (a) and left lateral (b) chest radiographs show a mass in the right lower lobe. (c) Contrast material-enhanced CT scan shows a heterogeneous right lower lobe mass with areas of low attenuation. (d) Photograph of the gross specimen demonstrates a yellowish cut surface related to the presence of fat. Scale is in centimeters. (e) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows proliferation of lipoblasts with vacuolation and nuclear pleomorphism.
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Figure 1e. Primary lung lipoblastic liposarcoma in a 42-year-old man who presented with mild dyspnea that had been worsening over the past 2 months. (a, b) Posteroanterior (a) and left lateral (b) chest radiographs show a mass in the right lower lobe. (c) Contrast material-enhanced CT scan shows a heterogeneous right lower lobe mass with areas of low attenuation. (d) Photograph of the gross specimen demonstrates a yellowish cut surface related to the presence of fat. Scale is in centimeters. (e) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) shows proliferation of lipoblasts with vacuolation and nuclear pleomorphism.
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Imaging Features.—
Although lung liposarcoma demonstrates nonspecific findings at conventional radiography (Fig 1a, Fig 1b), its CT appearance varies depending on the amount of fat within the mass. These varying CT appearances reflect the spectrum of pathologic patterns that occur. At unenhanced chest CT, liposarcoma is seen as a large, smoothly marginated mass. Unlike myxomatous and polymorphic liposarcomas, lipoblastic liposarcomas may demonstrate fat attenuation within the mass (Fig 1c) (8). To our knowledge, magnetic resonance (MR) imaging findings in lung liposarcoma have not been previously reported in the literature. However, it seems reasonable to assume that such findings would be similar to those in liposarcoma involving other organs. Other fat-containing lesions such as pulmonary lipoma, hamartoma, and lipoid pneumonia may be included in the differential diagnosis.
Benign Metastasizing Leiomyoma
Benign metastasizing leiomyoma is a very rare entity, with no more than 40 well-documented cases described in the literature (9). This entity was first reported in 1939 by Steiner (10) as metastasizing fibroleiomyoma. The term benign metastasizing leiomyoma is not widely accepted, and some pathologists argue that these tumors are actually metastatic low-grade leiomyosarcomas (11). Benign metastasizing leiomyoma almost invariably occurs in women, many of whom have a previous history of resected uterine leiomyomas that ranges from several years up to 20 years (10–15). Long-term prognosis is usually good (16,17).
Pathologic Features.—
At gross examination, benign metastasizing leiomyoma appears as single or multiple smooth, spheric, well-defined white nodules of different sizes. The cut surface may contain hemorrhagic areas.
It may be difficult to distinguish benign from malignant metastasizing leiomyoma even at histologic examination. Findings associated with malignant leiomyoma include an increased number of mitoses at histologic analysis (18,19). When the number of mitoses is greater than 10 per 10 high-power fields, the lesions are classified as leiomyosarcomas (18), but when the number is less than five, as occurs in the majority of cases, they are considered benign with an associated good prognosis (Fig 2b, 2c) (19).
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Figure 2a. Benign metastasizing leiomyoma in an asymptomatic 46-year-old woman with multiple pulmonary nodules and uterine leiomyomas. (a) CT scan obtained at the level of the right upper lobe bronchus shows three well-defined round lung nodules of different sizes. (b) Low-power photomicrograph (original magnification, x10; H-E stain) demonstrates a well-circumscribed nodule with collapse of the surrounding alveolar spaces. (c) Higher-power photomicrograph (original magnification, x20; H-E stain) shows that the nodules are composed of benign-appearing smooth muscle cells arranged in an interlacing pattern and intermingled with rich collagen bundles.
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Figure 2b. Benign metastasizing leiomyoma in an asymptomatic 46-year-old woman with multiple pulmonary nodules and uterine leiomyomas. (a) CT scan obtained at the level of the right upper lobe bronchus shows three well-defined round lung nodules of different sizes. (b) Low-power photomicrograph (original magnification, x10; H-E stain) demonstrates a well-circumscribed nodule with collapse of the surrounding alveolar spaces. (c) Higher-power photomicrograph (original magnification, x20; H-E stain) shows that the nodules are composed of benign-appearing smooth muscle cells arranged in an interlacing pattern and intermingled with rich collagen bundles.
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Figure 2c. Benign metastasizing leiomyoma in an asymptomatic 46-year-old woman with multiple pulmonary nodules and uterine leiomyomas. (a) CT scan obtained at the level of the right upper lobe bronchus shows three well-defined round lung nodules of different sizes. (b) Low-power photomicrograph (original magnification, x10; H-E stain) demonstrates a well-circumscribed nodule with collapse of the surrounding alveolar spaces. (c) Higher-power photomicrograph (original magnification, x20; H-E stain) shows that the nodules are composed of benign-appearing smooth muscle cells arranged in an interlacing pattern and intermingled with rich collagen bundles.
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Imaging Features.—
Radiographic features of metastasizing leiomyoma are nonspecific, with single or multiple well-circumscribed nodules throughout the lungs that may vary in size from microscopic to over 10 cm in diameter. CT similarly shows sharply marginated single or multiple nodules (Fig 2a). These lesions do not enhance after contrast material administration. Cavitation has been sporadically reported (15). A slow growth rate is typical of this tumor. The differential diagnosis must include metastases from other tumors, vascular lesions, and parasitic infestations such as hydatid disease (16).
Solitary Fibrous Tumor
Solitary fibrous tumor of the lung is a distinctive spindle cell neoplasm that most commonly arises in the pleura. However, this rare neoplasm has also been described at unusual sites unrelated to serosal cavities such as the lung (20), liver, thyroid gland, nasal cavities, and paranasal sinuses (21–23). Affected patients are usually asymptomatic, so that the tumor is discovered incidentally. Treatment of solitary fibrous tumor consists of surgical resection. The prognosis is excellent, with a low risk for recurrence or metastasis (24).
Pathologic Features.—
Solitary fibrous tumor manifests as a sharply circumscribed mass with a white whorled appearance on cut section. Despite its intrapulmonary location, this tumor demonstrates histologic findings that are identical to those in solitary fibrous tumor of the pleura. There is a haphazard growth of short spindly or plump cells with scanty cytoplasm that are intimately admixed with collagen (Fig 3c). Immunohistochemical analysis shows positivity for CD34 antigen, a finding that is highly diagnostic for this entity (21,22).
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Figure 3a. Solitary fibrous tumor of the lung in an asymptomatic 47-year-old man. (a) Localized posteroanterior chest radiograph shows a well-defined right lower lobe nodule. (b) CT scan (lung windowing) shows a nonspecific, well-circumscribed nodule. (c) Photomicrograph (original magnification, x40; H-E stain) shows multiple oval to spindle-shaped cells lacking nuclear atypia with abundant extracellular collagen deposition (*).
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Figure 3b. Solitary fibrous tumor of the lung in an asymptomatic 47-year-old man. (a) Localized posteroanterior chest radiograph shows a well-defined right lower lobe nodule. (b) CT scan (lung windowing) shows a nonspecific, well-circumscribed nodule. (c) Photomicrograph (original magnification, x40; H-E stain) shows multiple oval to spindle-shaped cells lacking nuclear atypia with abundant extracellular collagen deposition (*).
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Figure 3c. Solitary fibrous tumor of the lung in an asymptomatic 47-year-old man. (a) Localized posteroanterior chest radiograph shows a well-defined right lower lobe nodule. (b) CT scan (lung windowing) shows a nonspecific, well-circumscribed nodule. (c) Photomicrograph (original magnification, x40; H-E stain) shows multiple oval to spindle-shaped cells lacking nuclear atypia with abundant extracellular collagen deposition (*).
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Imaging Features.—
At radiologic examination, solitary fibrous tumor of the lung typically manifests as a round or oval intrapulmonary nodule or mass of variable size (Fig 3a, 3b). Although to our knowledge there are no documented series in the literature concerning the CT characteristics of this unusual tumor, it seems reasonable to hypothesize that CT findings would not be different from those in solitary fibrous tumor of the pleura.
Inflammatory Myofibroblastic Tumor (Plasma Cell Granuloma)
Inflammatory myofibroblastic tumor of the lung is a rare, benign pseudotumor that was first described in 1973 by Bahadori and Liebow (25). Previously known as inflammatory pseudotumor, plasma cell granuloma, xanthoma, fibroxanthoma, histiocytoma, plasmacytoma, or solitary mast cell tumor (25–28), it affects individuals of all ages without any sex predilection. Although this tumor is most commonly encountered in the lung, gastrointestinal tract, and salivary glands (29), other locations such as the mediastinum (25,30), bronchial wall (31), and trachea (32,33) have also been reported. The cause is uncertain, although a hypersensitivity reaction has been suggested (28,34,35). The natural history of inflammatory myofibroblastic tumor is controversial, and some consider it a locally invasive low-grade neoplasm composed of myofibroblasts. Inflammatory myofibroblastic tumor is difficult to diagnose with transbronchial or transthoracic needle biopsy due to its variable cellular composition. Complete resection is recommended for both diagnosis and treatment (36).
Pathologic Features.—
At gross examination, this tumor manifests as a well-circumscribed, unencapsulated white-yellow mass, more frequently located in a lower lobe. At histologic analysis, it is characterized by polyclonal infiltration of normal plasma cells mixed with other inflammatory cells such as lymphocytes, histiocytes, neutrophils, and myofibroblasts (Fig 4c). Myofibroblasts were recently recognized as the principal spindle-cell type in this inflammatory disorder, leading to the term inflammatory myofibroblastic tumor (37–39).
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Figure 4a. Inflammatory myofibroblastic tumor in a 50-year-old man with dyspnea and cough. (a) Localized posteroanterior chest radiograph shows an ill-defined peripheral mass of the left lower lobe. (b) Contrast-enhanced CT scan demonstrates the peripheral mass in the left lower lobe. A small pleural effusion is also noted. (c) High-power photomicrograph (original magnification, x200; H-E stain) of the resected specimen shows an admixture of chronic inflammatory and proliferating mesenchymal cells with a predominant plasma cell component.
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Figure 4b. Inflammatory myofibroblastic tumor in a 50-year-old man with dyspnea and cough. (a) Localized posteroanterior chest radiograph shows an ill-defined peripheral mass of the left lower lobe. (b) Contrast-enhanced CT scan demonstrates the peripheral mass in the left lower lobe. A small pleural effusion is also noted. (c) High-power photomicrograph (original magnification, x200; H-E stain) of the resected specimen shows an admixture of chronic inflammatory and proliferating mesenchymal cells with a predominant plasma cell component.
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Figure 4c. Inflammatory myofibroblastic tumor in a 50-year-old man with dyspnea and cough. (a) Localized posteroanterior chest radiograph shows an ill-defined peripheral mass of the left lower lobe. (b) Contrast-enhanced CT scan demonstrates the peripheral mass in the left lower lobe. A small pleural effusion is also noted. (c) High-power photomicrograph (original magnification, x200; H-E stain) of the resected specimen shows an admixture of chronic inflammatory and proliferating mesenchymal cells with a predominant plasma cell component.
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Imaging Features.—
The radiologic appearance of this tumor is typically that of a solitary, slow-growing circumscribed mass of variable size with a lobulated or spiculated border (Fig 4a, Fig 4b). Rarely, multiple masses occur (31), and sometimes diffuse pneumonitis or atelectasis is seen, probably related to compression of a proximal bronchus (40). Calcification is unusual, occurring more frequently in children (26,37,41). Cavitation is also rare (42). CT features, including patterns of contrast enhancement and calcification, have been characterized as variable and nonspecific (26,43).
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Epithelial Tumors
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Recurrent respiratory papillomatosis is an uncommon condition, usually related to human papilloma virus infection. It commonly affects preadolescent children. The majority of cases are uncomplicated, with lesions remaining localized to the laryngeal and subglottic region. Lung lesions are seen in less than 1% of affected patients and may occur after 10 years of laryngeal involvement (44,45). Factors that increase the risk of pulmonary involvement include diffuse viral contamination with resultant multicentric papillomas and tracheobronchial dissemination of fragments related to tracheotomy or surgical microexcision (46,47). Unlike uncomplicated laryngeal papillomatosis, pulmonary papillomatosis does not regress spontaneously (48,49). Pulmonary involvement may run a fulminant course and may carry a poor prognosis because of progressive respiratory insufficiency and life-threatening infections (45,50–52). The clinical findings of dyspnea, hemoptysis, and obstructive pneumonia vary depending on the number of papillomas and their anatomic location. Squamous cell carcinoma has been reported in 2% of patients with pulmonary involvement (46,48,53,54). Prognosis for patients with pulmonary papillomatosis is poor. Although interferon may occasionally be effective, treatment is palliative once the disease becomes disseminated. Progression of disease may lead to respiratory failure and death. Because of the increased risk of carcinoma, any change in the CT appearance of pulmonary lesions requires biopsy to rule out malignancy.
Pathologic Features
At gross examination, pulmonary parenchymal papillomatosis manifests as multiple large cavities lined with numerous papillomas that appear as cauliflower-like excrescences or small solid nodules. Distal bronchiectasis with atelectasis or consolidation of the peripheral lung may occur (55). At light microscopy, pulmonary papillomatosis most often displays a typical arrangement that varies from solid clusters of squamous cells within alveoli to larger cavitary lesions lined with flat, nonkeratinizing squamous epithelium. When cytologic atypia is present, differentiation from squamous cell carcinoma can be difficult (55).
Imaging Features
Radiologic findings in pulmonary papillomatosis are varied. The disease usually manifests as multiple well-defined, round, slow-growing solid or cystic nodules. Cystic lesions may exhibit thick or thin walls (Fig 5). Occasionally, large distal intrabronchial papillomas cause obstructive radiologic abnormalities including atelectasis, pneumonia, abscess, or bronchiectasis. A case of pneumothorax has been reported (56).
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Figure 5a. Pulmonary papillomatosis in a 14-year-old boy with cough and hemoptysis. (a) CT scan through the upper lobes (lung windowing) demonstrates a small tracheal nodule (arrowhead) representing a tracheal papilloma. (b) CT scan through the lower chest shows multiple cavitating lung nodules, some with air-fluid levels, representing pulmonary papillomatosis. (Fig 5 courtesy of J. Badosa, MD, Hospital Sant Joan de Deu, Barcelona, Spain.)
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Figure 5b. Pulmonary papillomatosis in a 14-year-old boy with cough and hemoptysis. (a) CT scan through the upper lobes (lung windowing) demonstrates a small tracheal nodule (arrowhead) representing a tracheal papilloma. (b) CT scan through the lower chest shows multiple cavitating lung nodules, some with air-fluid levels, representing pulmonary papillomatosis. (Fig 5 courtesy of J. Badosa, MD, Hospital Sant Joan de Deu, Barcelona, Spain.)
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Tumors of the Lymphoreticular System
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Angiocentric Lymphoma (Lymphomatoid Granulomatosis)
Angiocentric lymphoma was previously called lymphomatoid granulomatosis because it was considered a form of necrotizing vasculitis similar to Wegener granulomatosis, with a propensity to progress to malignant lymphoma (57,58). The current consensus is that lymphomatoid granulomatosis is a distinctive polymorphic form of angiocentric lymphoma. Recently, polymerase chain reaction and immunohistochemical studies have shown that many angiocentric lymphomas are actually Epstein-Barr virus–positive B-cell lymphomas (57,59–61).
Angiocentric lymphoma has a predilection for extranodal involvement, most frequently of the lung (57). Extrathoracic manifestations are common and include skin involvement in 37% of cases and central and peripheral nervous system involvement in 30% (62–64). The prognosis is poor, and patients do not survive more than 2 years (59).
Pathologic Features.—
Gross pathologic findings are characterized by nodular consolidations up to 10 cm in diameter. These nodular lesions have a "fish flesh" appearance on cut section and are commonly associated with central necrosis and cavitation.
At histologic analysis, angiocentric lymphoma is characterized by the presence of nodular and diffuse interstitial infiltration by lymphoid cells. This infiltration tends to have an angiocentric and angiodestructive pattern (Fig 6b). As the nodules enlarge, central necrosis and cavitation develop. A large vessel may be present in the center of the nodule as well as infiltration by lymphoid cells, justifying the descriptive designation of angiocentric lymphoma. Immunohistochemical studies show that most of the lymphoid cells are CD4-positive T cells (59).
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Figure 6a. Angiocentric lymphoma in a 65-year-old woman with shortness of breath and cough. (a) Posteroanterior chest radiograph shows multiple large, ill-defined masses in both lungs. (b) High-power photomicrograph (original magnification, x400; H-E stain) shows pulmonary lymphoma with extensive vascular infiltration and severe luminal narrowing.
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Figure 6b. Angiocentric lymphoma in a 65-year-old woman with shortness of breath and cough. (a) Posteroanterior chest radiograph shows multiple large, ill-defined masses in both lungs. (b) High-power photomicrograph (original magnification, x400; H-E stain) shows pulmonary lymphoma with extensive vascular infiltration and severe luminal narrowing.
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Imaging Features.—
Radiographic findings are variable, depending on the stage of the disease. Typically, there are nonspecific bilateral soft-tissue nodules ranging from 1 to 5 cm in diameter and predominantly involving the lung bases (Fig 6a). Cavitary nodules are seen in approximately 25% of cases and are probably related to secondary infarction (57,62,65,66). Pleural effusion is seen in approximately 30% of patients (65).
Low-Grade Small B-Cell Lymphoma of BALT Origin (Pseudolymphoma)
Bronchus-associated lymphoid tissue (BALT) consists of subepithelial lymphoid follicles distributed along distal bronchi and bronchioles (67,68). Low-grade BALT lymphomas, sometimes called BALTomas, are slow-growing neoplasms, some of which were originally designated as pseudolymphomas on the basis of apparently benign clinicopathologic features (59,69). Patients range in age from 25 to 85 years, with both sexes being equally affected. Nearly 50% of patients are asymptomatic, so that the disease is discovered incidentally (70). Constitutional symptoms suggest extrathoracic involvement. The prognosis of BALT lymphoma depends on the predominant cell type and the disease stage. The treatment is local surgical excision, but recurrence is seen in 10%–15% of cases (70–72).
Pathologic Features.—
Gross pathologic findings in BALT lymphomas are characteristic, consisting of fleshy, nonnecrotic, whitish masses with infiltrative and nondestructive growth and preservation of the lung architecture (Fig 7b). At lightmicroscopy, BALT lymphomas most often display a typical lymphoepithelial pattern, with islands of epithelial cells densely infiltrated by lymphocytes (Figs 7c, 8b) (59).
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Figure 7a. Low-grade small B-cell lymphoma of BALT origin in a 69-year-old woman who had undergone left pneumectomy 10 years earlier for a left upper lobe pseudolymphoma. (a) Initial posteroanterior chest radiograph obtained prior to surgery demonstrates a large mass in the posterior portion of the left upper lobe. (b) Photograph of the surgical specimen demonstrates an oval parenchymal mass with a heterogeneous appearance on cut section. (c) High-power photomicrograph of the surgical specimen (original magnification, x200; H-E stain) shows a lymphoid infiltrate of small, well-differentiated lymphocytes that involves both parenchymatous and epithelial structures of the lung. (d) CT scan (lung windowing) obtained 10 years later shows multiple nodular lesions, many of which have a peribronchovascular distribution and contain air bronchograms.
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Figure 7b. Low-grade small B-cell lymphoma of BALT origin in a 69-year-old woman who had undergone left pneumectomy 10 years earlier for a left upper lobe pseudolymphoma. (a) Initial posteroanterior chest radiograph obtained prior to surgery demonstrates a large mass in the posterior portion of the left upper lobe. (b) Photograph of the surgical specimen demonstrates an oval parenchymal mass with a heterogeneous appearance on cut section. (c) High-power photomicrograph of the surgical specimen (original magnification, x200; H-E stain) shows a lymphoid infiltrate of small, well-differentiated lymphocytes that involves both parenchymatous and epithelial structures of the lung. (d) CT scan (lung windowing) obtained 10 years later shows multiple nodular lesions, many of which have a peribronchovascular distribution and contain air bronchograms.
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Figure 7c. Low-grade small B-cell lymphoma of BALT origin in a 69-year-old woman who had undergone left pneumectomy 10 years earlier for a left upper lobe pseudolymphoma. (a) Initial posteroanterior chest radiograph obtained prior to surgery demonstrates a large mass in the posterior portion of the left upper lobe. (b) Photograph of the surgical specimen demonstrates an oval parenchymal mass with a heterogeneous appearance on cut section. (c) High-power photomicrograph of the surgical specimen (original magnification, x200; H-E stain) shows a lymphoid infiltrate of small, well-differentiated lymphocytes that involves both parenchymatous and epithelial structures of the lung. (d) CT scan (lung windowing) obtained 10 years later shows multiple nodular lesions, many of which have a peribronchovascular distribution and contain air bronchograms.
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Figure 7d. Low-grade small B-cell lymphoma of BALT origin in a 69-year-old woman who had undergone left pneumectomy 10 years earlier for a left upper lobe pseudolymphoma. (a) Initial posteroanterior chest radiograph obtained prior to surgery demonstrates a large mass in the posterior portion of the left upper lobe. (b) Photograph of the surgical specimen demonstrates an oval parenchymal mass with a heterogeneous appearance on cut section. (c) High-power photomicrograph of the surgical specimen (original magnification, x200; H-E stain) shows a lymphoid infiltrate of small, well-differentiated lymphocytes that involves both parenchymatous and epithelial structures of the lung. (d) CT scan (lung windowing) obtained 10 years later shows multiple nodular lesions, many of which have a peribronchovascular distribution and contain air bronchograms.
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Figure 8a. Low-grade small B-cell lymphoma of BALT origin in a 59-year-old woman with Sjögren syndrome. (a) High-resolution CT scan reveals patchy areas of consolidation in the middle and lower lobes. An air bronchogram is clearly visible in one lesion. (b) High-power photomicrograph (original magnification, x200; H-E stain) of the lung surgical specimen reveals a low-grade B-cell lymphoma. Note the severe lymphocytic proliferation surrounding bronchioles (arrow).
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Figure 8b. Low-grade small B-cell lymphoma of BALT origin in a 59-year-old woman with Sjögren syndrome. (a) High-resolution CT scan reveals patchy areas of consolidation in the middle and lower lobes. An air bronchogram is clearly visible in one lesion. (b) High-power photomicrograph (original magnification, x200; H-E stain) of the lung surgical specimen reveals a low-grade B-cell lymphoma. Note the severe lymphocytic proliferation surrounding bronchioles (arrow).
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Imaging Features.—
Although most BALT lymphomas manifest as solitary, well-delineated soft-tissue masses (Fig 7a), their appearance can be quite variable. Less common imaging features include multiple unilateral or bilateral nodules, diffuse infiltrates along the bronchovascular bundles and interlobular septa, and extensive lobar infiltrates mimicking pneumonia. CT demonstrates airspace consolidation, nodules with air bronchograms (Figs 7d, 8a), or areas of ground-glass attenuation. Bubble-like areas of hypoattenuation have also been described (59,62,68,70, 71,73–75). In some patients, chest radiographic findings remain abnormal for several years before biopsy and definitive histologic diagnosis. Although hilar and mediastinal lymphadenopathy is not a prominent radiologic finding in BALT lymphomas, nodal involvement has been documented at pathologic analysis in 30% of cases (71,75).
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Neuroendocrine Tumors
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Large cell neuroendocrine carcinoma represents a high-grade neuroendocrine malignancy and is considered to be a distinct clinicopathologic entity (76–78). This tumor is most commonly seen in the 7th decade of life, with a median age at presentation of 63 years and a clear (4:1) male predilection. Clinical findings are nonspecific, and patients usually present with cough, hemoptysis, dyspnea, or chest pain. Findings associated with ectopic hormone production have also been reported. Whenever possible, surgical excision and adjunct chemotherapy remain the treatment of choice. Large cell neuroendocrine carcinoma has a poor prognosis, with survival rates similar to those of oat cell carcinoma (79).
Pathologic Features
At gross examination, these tumors are large pulmonary masses with a yellow-white to tan-white surface. Central necrosis may be seen (80). At histologic analysis, the tumor is characterized by large polygonal or fusiform cells with a fine granular cytoplasm. Rosette-like structures may be present (80). Histologic criteria for the diagnosis of large cell neuroendocrine carcinomas include neuroendocrine appearance at light microscopy (organoid, trabecular, or rosette-like patterns), large polygonal tumor cells, fine eosinophilic cytoplasm, coarse chromatin, high mitotic rate (Fig 9b), frequent necrosis, and neuroendocrine features at immunohistochemical analysis (78).
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Figure 9a. Large cell neuroendocrine carcinoma in a 69-year-old man with nonproductive cough and weight loss. (a) Contrast-enhanced CT scan obtained at the level of the aortic arch demonstrates a mass with punctate calcifications (arrowhead) and low-attenuation areas related to necrosis. Right paratracheal lymphadenopathies are also demonstrated. (b) Low-power photomicrograph (original magnification, x40; H-E stain) shows oval and spindle-shaped tumor cells with frequent mitoses (arrow). The abundant cytoplasm and vesicular chromatin favor the diagnosis of a non-small cell carcinoma.
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Figure 9b. Large cell neuroendocrine carcinoma in a 69-year-old man with nonproductive cough and weight loss. (a) Contrast-enhanced CT scan obtained at the level of the aortic arch demonstrates a mass with punctate calcifications (arrowhead) and low-attenuation areas related to necrosis. Right paratracheal lymphadenopathies are also demonstrated. (b) Low-power photomicrograph (original magnification, x40; H-E stain) shows oval and spindle-shaped tumor cells with frequent mitoses (arrow). The abundant cytoplasm and vesicular chromatin favor the diagnosis of a non-small cell carcinoma.
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Imaging Features
At radiography, large cell neuroendocrine carcinomas appear as peripheral, well-marginated round or oval masses. CT demonstrates a well-defined, heterogeneous mass that may contain punctate calcification. Heterogeneous contrast material enhancement results from intratumoral necrosis (Fig 9a). Mediastinal lymph node enlargement is usually present (77,81).
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Vascular Tumors
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Epithelioid Hemangioendothelioma (Intravascular Bronchioloalveolar Tumor)
Epithelioid hemangioendothelioma, previously called intravascular bronchioloalveolar tumor (82,83), is a rare pulmonary neoplasm, with less than 40 cases described worldwide (84). Although epithelioid hemangioendothelioma has been reported in patients of all age groups (age range at presentation, 12–61 years), 40% of patients are under 30 years of age (84). Clinical presentation varies depending on the location of the tumor and the structures it affects. Patients are usually asymptomatic, or they may present with mild cough, dyspnea, chest pain, or weight loss. The clinical course of affected patients varies widely; many tumors behave in a benign fashion, whereas others are highly malignant. A poor prognosis has been associated with severe symptoms and with airway, vascular, and pleural involvement (85,86).
Pathologic Features.—
At gross examination, epithelioid hemangioendotheliomas of the lung are discrete, circumscribed, firm gray-white nodules that may resemble amyloid or cartilage. At histologic analysis, these nodules demonstrate a hyalinized center and a cellular advancing edge that extends into alveolar spaces, bronchioles, vessels, and lymphatic vessels (Fig 10c). Some lesions may demonstrate moderate atypia, necrosis, and mitoses. Indeed, these tumors are considered low-grade sclerosing angiosarcomas (87).
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Figure 10a. Epithelioid hemangioendothelioma of the lung in a 16-year-old girl with mild dyspnea and cough over the past 2 months. (a) CT scan through the upper lobes (lung windowing) shows multiple bilateral small lung nodules with irregular margins. (b) Contrast-enhanced liver CT scan demonstrates two partially calcified nodules (arrows) associated with hepatic capsular retraction representing epithelioid hemangioendotheliomas. (c) High-power photomicrograph (original magnification, x400; H-E stain) shows the intravascular proliferation of tumoral nidi with central hyalinization (arrows).
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Figure 10b. Epithelioid hemangioendothelioma of the lung in a 16-year-old girl with mild dyspnea and cough over the past 2 months. (a) CT scan through the upper lobes (lung windowing) shows multiple bilateral small lung nodules with irregular margins. (b) Contrast-enhanced liver CT scan demonstrates two partially calcified nodules (arrows) associated with hepatic capsular retraction representing epithelioid hemangioendotheliomas. (c) High-power photomicrograph (original magnification, x400; H-E stain) shows the intravascular proliferation of tumoral nidi with central hyalinization (arrows).
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Figure 10c. Epithelioid hemangioendothelioma of the lung in a 16-year-old girl with mild dyspnea and cough over the past 2 months. (a) CT scan through the upper lobes (lung windowing) shows multiple bilateral small lung nodules with irregular margins. (b) Contrast-enhanced liver CT scan demonstrates two partially calcified nodules (arrows) associated with hepatic capsular retraction representing epithelioid hemangioendotheliomas. (c) High-power photomicrograph (original magnification, x400; H-E stain) shows the intravascular proliferation of tumoral nidi with central hyalinization (arrows).
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Imaging Features.—
The most characteristic radiologic feature of epithelioid hemangioendothelioma of the lung is the presence of multiple small (usually <3-cm-diameter) nodules in both lungs. The lesion borders are well circumscribed or slightly ill-defined (Fig 10a). Occasionally, there is an associated pleural effusion (88,89). The differential diagnosis must include pulmonary granulomatous diseases and lung metastases.
Hemangiopericytoma
Primary pulmonary hemangiopericytoma is an infrequent malignancy, with less than 100 reported cases (90–93). These tumors arise from the so-called Zimmermann cells (ie, pericytes around small blood vessels) (94–96). Most patients are in the 5th or 6th decade of life. Patients are frequently asymptomatic, and both sexes are affected equally (90,91,96,97), However, symptoms (when present) do not differ from those of lung cancer or other pulmonary tumors. Hypoglycemia has been reported as a paraneoplastic syndrome (98). The treatment is wide resection, and the prognosis is uncertain. Criteria for malignancy are not well established, but adverse prognostic factors include a size greater than 8 cm, pleural or bronchial invasion, angiolymphatic invasion, and more than three mitoses per 10 high-power fields (91).
Pathologic Features.—
At gross examination, the tumors are fleshy masses that may exhibit hemorrhage and necrosis. At histologic analysis, they display a vascular pattern with small, thin-walled branching sinusoidal spaces resembling a stag’s horns (Fig 11b) (91).
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Figure 11a. Lung hemangiopericytoma in an asymptomatic 52-year-old woman. (a) Posteroanterior chest radiograph demonstrates a well-defined right upper lobe mass, which was discovered incidentally. (b) Low-power photomicrograph (original magnification, x40; H-E stain) demonstrates uniform spindle cells arranged around dilated "staghorn" vessels (*).
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Figure 11b. Lung hemangiopericytoma in an asymptomatic 52-year-old woman. (a) Posteroanterior chest radiograph demonstrates a well-defined right upper lobe mass, which was discovered incidentally. (b) Low-power photomicrograph (original magnification, x40; H-E stain) demonstrates uniform spindle cells arranged around dilated "staghorn" vessels (*).
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Imaging Features.—
At chest radiography, the tumor manifests as a sharply defined, central or peripheral solitary pulmonary nodule (Fig 11a) (93). CT may demonstrate a heterogeneous mass with or without central necrosis. Calcification is rare (92).
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Nonneoplastic Lesions (Pseudotumors)
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Nodular Pulmonary Amyloid (Amyloidoma)
Amyloidosis refers to a group of disorders characterized by the deposition of abnormal protein material in extracellular tissue. This protein takes up Congo red stain and exhibits apple-green birefringence at polarized microscopic analysis (99). Amyloid deposition can occur in association with inflammatory, hereditary, or neoplastic entities.
Pulmonary involvement by amyloid may be localized or diffuse and may have a variety of appearances. Primary pulmonary amyloid takes at least three forms: tracheobronchial, nodular parenchymal, and alveolar septal, the latter being the least common (100–104).
Nodular pulmonary amyloidosis is a limited form of amyloidosis characterized by one or more intrapulmonary nodules or masses (amyloidomas). Because of their nodular appearance, amyloidomas are usually misconstrued as neoplasms (105). They may be single or multiple, may calcify or undergo osseous metaplasia, and occur more frequently in the lower lobes. On average, affected patients are in the 6th decade of life (99,103,106–109). Resection of these nodules is both diagnostic and curative.
Pathologic Features.—
At gross examination, amyloid nodules are firm and either yellow, gray, or pale tan. The nodules range in size from 0.6 to 15 cm. Larger lesions may cavitate or exhibit hemorrhage, necrosis, fibrosis, or calcification (105). At histologic analysis, amyloid appears as an amorphous sheet of eosinophilic extracellular material that surrounds vessels (Fig 12c, Fig 12d).
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Figure 12a. Nodular lung amyloidosis in a 70-year-old man with mild dyspnea. (a) Localized posteroanterior chest radiograph shows a juxtamediastinal right upper lobe mass. (b) CT scan obtained at the level of the supraaortic arches (mediastinal windowing) reveals a juxtaspinal solid mass with amorphous calcification (arrow) in the right upper lobe. (c) Low-power photomicrograph (original magnification, x10; Congo red stain) shows irregular nodular masses of amyloid replacing the lung parenchyma. (d) On a polarized microscopic image (Congo red stain), the amyloid exhibits typical apple-green birefringence.
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Figure 12b. Nodular lung amyloidosis in a 70-year-old man with mild dyspnea. (a) Localized posteroanterior chest radiograph shows a juxtamediastinal right upper lobe mass. (b) CT scan obtained at the level of the supraaortic arches (mediastinal windowing) reveals a ju | |
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Abstract
LEARNING OBJECTIVES
